Computer simulations of the signalling network in FLT3 ⁺-acute myeloid leukaemia - indications for an optimal dosage of inhibitors against FLT3 and CDK6.

ABSTRACT:

Background

Mutations in the FMS-like tyrosine kinase 3 (FLT3) are associated with uncontrolled cellular functions that contribute to the development of acute myeloid leukaemia (AML). We performed computer simulations of the FLT3-dependent signalling network in order to study the pathways that are involved in AML development and resistance to targeted therapies.

Results

Analysis of the simulations revealed the presence of alternative pathways through phosphoinositide 3 kinase (PI3K) and SH2-containing sequence proteins (SHC), that could overcome inhibition of FLT3. Inhibition of cyclin dependent kinase 6 (CDK6), a related molecular target, was also tested in the simulation but was not found to yield sufficient benefits alone.

Conclusions

The PI3K pathway provided a bas

SUBMITTER: Buetti-Dinh A 

PROVIDER: S-EPMC5921566 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature